Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced Poorly Differentiated (G3) Non-Small Cell Gastrointestinal Neuroendocrine Carcinomas
概览
- 阶段
- 2 期
- 干预措施
- Capecitabine
- 疾病 / 适应症
- Gastric Neuroendocrine Carcinoma
- 发起方
- ECOG-ACRIN Cancer Research Group
- 入组人数
- 67
- 试验地点
- 1344
- 主要终点
- PFS
- 状态
- 进行中（未招募）
- 最后更新
- 昨天
概览
简要总结
This randomized phase II trial studies how well temozolomide and capecitabine work compared to standard treatment with cisplatin or carboplatin and etoposide in treating patients with neuroendocrine carcinoma of the gastrointestinal tract or pancreas that has spread to other parts of the body (metastatic) or cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, capecitabine, cisplatin, carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Certain types of neuroendocrine carcinomas may respond better to treatments other than the current standard treatment of cisplatin and etoposide. It is not yet known whether temozolomide and capecitabine may work better than cisplatin or carboplatin and etoposide in treating patients with this type of neuroendocrine carcinoma, called non-small cell neuroendocrine carcinoma.
详细描述
PRIMARY OBJECTIVES: I. To assess the progression free survival (PFS) of platinum (cisplatin or carboplatin) and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. SECONDARY OBJECTIVES: I. To assess the response rate (RR) of platinum (cisplatin or carboplatin) and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. II. To assess the overall survival (OS) of platinum (cisplatin or carboplatin) and etoposide versus the OS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. III. To evaluate the toxicities associated with the combination of temozolomide and capecitabine and the combination of platinum (cisplatin or carboplatin) and etoposide, respectively, in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. TERTIARY OBJECTIVES: I. To assess the impact of each treatment regimen on PFS, RR and OS based on marker of proliferation Ki-67 index in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas. (Laboratory) II. To assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment. (Laboratory) III. To assess the agreement in Ki-67 status between that reported by institutional pathologist and that reported by central pathology review. (Laboratory) OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14 and temozolomide PO once daily (QD) on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cisplatin intravenously (IV) on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
研究者
入排标准
入选标准
- •Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of gastrointestinal (GI) origin; primary tumors arising from the lung, gynecologic organs or prostate are not permitted
- •Patients must have pathologically/histologically confirmed tumor of non-small cell histology
- •Patients must have a Ki-67 proliferative index of 20-100% OR at least 10 mitotic figures per 10 high powered fields
- •Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained within 4 weeks prior to randomization and must be acquired by multiphasic computed tomography (CT) or contrast magnetic resonance imaging (MRI)
- •NOTE: positron emission tomography (PET)-CT scans are allowed provided the CT portion of the exam is equivalent to a diagnostic CT scan and includes both oral and IV contrast
- •Any prior surgeries must have been completed at least 4 weeks prior to randomization
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Patients may not be receiving any other investigational agents while on study treatment
- •Patients may not be receiving Coumadin while on treatment; other anticoagulants are allowed
- •Leukocytes \>= 3,000/mm\^3
排除标准
- •Patients may not have had any prior systemic treatment for this malignancy (for example chemotherapy or somatostatin analogues); prior palliative radiation is permitted but radiated lesions may not be used for measurement
- •Patients may not have received any of the protocol agents within 5 years prior to randomization
- •Patients with brain metastases (either remote or current) or presence of carcinomatous meningitis are not eligible
- •Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency will be excluded
- •Patients must NOT have active or uncontrolled infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia or a serious psychiatric illness/social situation that would limit compliance with study requirements
- •Patients must NOT have a history of allergic reactions attributed to compounds of similar chemical or biochemical composition to cisplatin, carboplatin, etoposide, temozolomide or capecitabine
- •Patients must NOT have absorption issues that would limit the ability to absorb study agents
- •Patients with a history of the following within =\< 12 months of study entry are not eligible:
- •Arterial thromboembolic events
- •Unstable angina
研究组 & 干预措施
Arm A (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Capecitabine
Arm A (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
Arm A (capecitabine, temozolomide)
Patients receive capecitabine PO BID on days 1-14 and temozolomide PO QD on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Temozolomide
Arm B (cisplatin, carboplatin, etoposide)
Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin
Arm B (cisplatin, carboplatin, etoposide)
Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin
Arm B (cisplatin, carboplatin, etoposide)
Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide
Arm B (cisplatin, carboplatin, etoposide)
Patients receive cisplatin IV on days 1-3 or carboplatin IV on day 1. Patients also receive etoposide IV on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis
结局指标
主要结局
PFS
时间窗: Time from randomization to documented progression or death without progression, assessed up to 1 year
Kaplan-Meier estimates will be used for time-to-event distribution. PFS by arm will be compared using one-sided stratified log-rank tests. Stratified Cox?s proportional hazards models will be used to estimate hazard ratios.
Progression-free Survival (PFS)
时间窗: assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years from randomization until disease progression, up to 5 years from study registration
PFS is defined as the time from randomization to documented progression or death without progression. PFS is censored at the date of last disease evaluation. The study was closed for futility in 2021 after the 2021 Spring DSMC meeting, which found that the boundary for futility had been met (ie, temozolomide and capecitabine did not appear to be superior to platinum and etoposide chemotherapy). As the interim analysis finding led to the conclusion of the study, no PFS stratified logrank test was conducted with the data extracted on April 23rd, 2025 for the final analysis, that was presented here.
次要结局
- Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 30 days after last dose of protocol therapy)
- OS(Time from randomization to death from any cause, assessed up to 5 years)
- Response rate (complete response or partial response) by RECIST 1.1(Up to 5 years)
- Overall Survival (OS)(assessed at baseline, then every 3 months within 2 years from randomization, and every 6 months if patient is 3-5 years from randomization, up to 5 years from randomization)
- Objective Response Rate (ORR)(assessed at baseline, every 8 weeks until treatment completion, then every 3 months within 2 years and every 6 months within 3-5 years, up to 5 years from registration; the best response among all assessments was considered as objective response)